Abstract：
BACKGROUND:This phase 1 study examined the safety, maximum-tolerated dose (MTD) and antitumour activity of E7449, a novel PARP 1/2 and tankyrase 1/2 inhibitor. METHODS:E7449 was orally administered once daily in 28-day cycles to patients with advanced solid tumours (50-800-mg doses). Archival tumour samples from consenting patients were evaluated for the expression of 414 genes in a biomarker panel (2X-121 drug-response predictor [DRP]) found to be predictive of the response to E7449 in cell lines. RESULTS:Forty-one patients were enrolled (13 pancreatic, 5 ovarian, 4 each with breast, lung or colorectal cancer and 11 with other tumour types). The most common grade ≥3 treatment-related adverse event was fatigue (n = 7, 17.1%). Five patients experienced a dose-limiting toxicity (fatigue, n = 4, 800 mg; anaphylaxis, n = 1, 600 mg) for an MTD of 600 mg. E7449 exhibited antitumour activity in solid tumours, including 2 partial responses (PRs), and stable disease (SD) in 13 patients, which was durable (>23 weeks) for 8 patients. In 13 patients, the 2X-121 DRP identified those achieving PR and durable SD. E7449 showed good tolerability, promising antitumour activity and significant concentration-dependent PARP inhibition following 50-800-mg oral dosing. CONCLUSION:The results support further clinical investigation of E7449 and its associated biomarker 2X-121 DRP. CLINICAL TRIAL REGISTRATION:www.ClinicalTrials.gov code: NCT01618136.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Plummer R,Dua D,Cresti N,Drew Y,Stephens P,Foegh M,Knudsen S,Sachdev P,Mistry BM,Dixit V,McGonigle S,Hall N,Matijevic M,McGrath S,Sarker Ddoi
10.1038/s41416-020-0916-5subject
Has Abstractpub_date
2020-08-01 00:00:00pages
525-533issue
4eissn
0007-0920issn
1532-1827pii
10.1038/s41416-020-0916-5journal_volume
123pub_type
杂志文章abstract：:The present study was designed to examine whether different p53 haplotypes of exon 4-intron 3-intron 6 affect the frequency of mutations and loss of heterozygosity (LOH) of the p53 gene in male oral squamous cell carcinomas (OSCCs) in Taiwan. We found that individuals without two Pro-W-G alleles had significantly high...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6602271
更新日期：2005-01-17 00:00:00
abstract：:The distribution of labelled cells through 5 different mouse tumours was measured after a single injection of [3H]-thymidine [( 3H]-TdR) or [3H]-deoxyuridine [( 3H]-UdR). All the tumours had areas where the percentage of labelled cells (the labelling index, LI) was high and areas where the LI was very low. The total a...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1985.3
更新日期：1985-01-01 00:00:00
abstract：:Two cell lines (2-10-1 and 8-10-2) derived by exposure to primary tracheal explants to MNNG in vitro were not tumorigenic in syngeneic F-344 rats or athymic BALB/c (nu/nu) mice at early passage, but became tumorigenic at late passage. These cell lines are therefore suited to study the expression of neoantigens during ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1981.176
更新日期：1981-08-01 00:00:00
abstract：:The registered incidence rate of childhood central nervous system (CNS) tumours has increased in several countries. It is uncertain whether these increases are biologically real or owing to improved diagnostic methods. We explored the medical records of 626 CNS tumours diagnosed in Danish children between 1980 and 199...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6603278
更新日期：2006-08-07 00:00:00
abstract：:Intra-tumoural heterogeneity of proliferation has been assessed by taking multiple biopsies from 30 colorectal cancers. Following in vivo IUDR labelling, dual parameter flow cytometry was used to measure tumour DNA index (DI) and labelling index (LI) and to derive DNA synthesis time (Ts) and potential doubling time (T...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1993.376
更新日期：1993-09-01 00:00:00
abstract：:Darbepoetin alfa is a novel erythropoiesis stimulating protein (NESP), which stimulates erythropoiesis by the same mechanism as recombinant human erythropoietin (rHuEPO). NESP has been shown to be safe and efficacious in patients with chronic renal failure. NESP is biochemically distinct from rHuEPO, due to its increa...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章,多中心研究
doi：10.1054/bjoc.2001.1748
更新日期：2001-04-01 00:00:00
abstract：:The zinc finger protein glioma-associated oncogene homologue 1 (Gli-1) is a critical component of the Hedgehog (Hh) signalling pathway, which is essential for morphogenesis and stem-cell renewal, and is dysregulated in many cancer types. As data were not available on the role of Gli-1 expression in oesophageal cancer ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6604361
更新日期：2008-05-20 00:00:00
abstract：:Endogamous groups in Western India have been known to have a wide degree of genetic diversity. Analysis of the data available on some of the endogamous groups belonging to two main communities attending the Tata Memorial Hospital, Bombay, viz. Hindus from Maharashtra, and Hindus from Gujarat show that one of the endog...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1971.77
更新日期：1971-12-01 00:00:00
abstract：:The clearance of an intradermally-injected solution of 133Xenon in 0.9% saline has been used to study the impairment and recovery of blood flow in mouse tail for 5 days following photodynamic therapy (PDT) with 2mg TPPS i.v. per mouse and a range of doses of white light. Impairment of blood flow was observed within 10...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1988.105
更新日期：1988-05-01 00:00:00
abstract：:Magnetic resonance spectroscopy was used to study intracellular pH and compounds which contain phosphorus in normal human brain and primary brain tumours non-invasively. In normal subjects (n = 7) intracellular pH (pHi) of the brain was 7.03 +/- 0.02 (mean +/- s.e.m.). The pHi did not vary between superficial (2 cm, m...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1989.300
更新日期：1989-09-01 00:00:00
abstract：:Cytogenetic investigation was performed on direct preparations of 15 endometrial cancers showing different histotypes. Clonal abnormalities were found in 11 out of 13 analysable cases. The modal chromosome number was near diploid in all cases. The abnormal karyotypes contained relatively simple numerical or structural...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1997.312
更新日期：1997-01-01 00:00:00
abstract：:Human pancreatic exocrine adenocarcinoma cells established in tissue culture expressed both HLA and beta 2-microglobulin (beta 2M). Plasma-membrane components of this pancreatic cancer cell line were purified from plasma membrane fractions enriched by sucrose density-gradient centrifugation, using immunoaffinity chrom...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1979.250
更新日期：1979-11-01 00:00:00
abstract：BACKGROUND:Preoperative radiotherapy (RT) is commonly used to treat localised soft-tissue sarcomas (STS). Hypoxia is an important determinant of radioresistance. Whether antiangiogenic therapy can 'normalise' tumour vasculature, thereby improving oxygenation, remains unknown. METHODS:Two cohorts were prospectively enr...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2014.537
更新日期：2014-12-09 00:00:00
abstract：:Epithelial cadherin (E-CD) is a member of the cadherin family of cell adhesion molecules and has been implicated as an invasion suppressor molecule in vitro and in vivo. We analysed 174 breast tumours from the Nottingham/Tenovus Breast Cancer Series immunohistochemically for E-CD expression using the mouse monoclonal ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.2001.2178
更新日期：2001-12-14 00:00:00
abstract：:Bispecific antibodies (bsAb) are considered as promising tools for the elimination of disseminated tumour cells in a minimal residual disease situation. The bsAb-mediated recruitment of an immune effector cell in close vicinity of a tumour cell is thought to induce an antitumoural immune response. However, classical b...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.2000.1237
更新日期：2000-07-01 00:00:00
abstract：:The level of expression of keratinocyte growth factor (KGF) mRNA has been measured in human breast cell lines, purified populations of epithelial cells, myoepithelial cells and fibroblasts from reduction mammoplasty tissue and a panel of 42 breast cancers and 30 non-malignant human breast tissues using a semiquantitat...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1997.269
更新日期：1997-01-01 00:00:00
abstract：:Complex biological pathways including angiogenesis, invasion, osteoclastic activation and bone matrix degradation are involved in the formation of bone metastasis (BM). The aim of our study was to investigate the cross-sectional and longitudinal associations of a panel of 12 serum biochemical markers reflecting biolog...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6603285
更新日期：2006-08-21 00:00:00
abstract：:Incidence and mortality data, stage of disease and treatment information for female breast cancer were obtained for the years 1975-1999 for the former Yorkshire Regional Health Authority area, from the Northern and Yorkshire Cancer Registry and Information Service. Deaths by age group and 3-year calendar period were s...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6601614
更新日期：2004-02-09 00:00:00
abstract：:NIH3T3 cells transfected with c-H-ras and/or c-myc genes were examined for differences in drug sensitivity. The five transfectants used were N8, NIH3T3-nm-1, pT22-3-nm-2, pP1-4 and pT22-3. They were transfected with pKOneo alone, pKOneo and c-myc, pKOneo and c-myc plus activated c-H-ras, normal c-H-ras and activated c...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1991.56
更新日期：1991-02-01 00:00:00
abstract：BACKGROUND:Metastatic clear cell renal cell carcinoma (ccRCC) patients have <9% 5-year survival rate, do not respond well to targeted therapy and eventually develop resistance. A better understanding of molecular pathways of RCC metastasis is the basis for the discovery of novel prognostic markers and targeted therapie...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2013.828
更新日期：2014-03-04 00:00:00
abstract：:The objective of this study was to document the occurrence and to correlate the prevalence of different human papillomavirus (HPV) types with the cytological results on simultaneously performed thin-layer preparations in a large population of Flemish women. During 1 year, 69 290 thin-layer preparations were interprete...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6600756
更新日期：2003-02-24 00:00:00
abstract：:Women with a family history of breast cancer generally self-refer because they have a feeling that their risk is high. However, they have, in general, only a hazy notion of the population risk of breast cancer and their own risk in relation to this. It is probable that they are helped by genetic counselling and, if at...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1994.423
更新日期：1994-11-01 00:00:00
abstract：BACKGROUND:Temsirolimus was approved in Europe as first-line treatment of poor-prognosis advanced renal cell carcinoma (advRCC) based on significant clinical benefits. METHODS:Patients with advRCC and multiple poor-prognostic factors were randomly assigned to receive 25 mg intravenous temsirolimus weekly, interferon-a...
journal_title：British journal of cancer
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1038/sj.bjc.6605647
更新日期：2010-05-11 00:00:00
abstract：:Even though the majority of patients with bladder malignancies initially present with low stage disease, the clinical epidemiology of these so-called superficial bladder tumours is not well known. In this paper, disease characteristics at initial presentation and during follow-up are described in 1,745 primary cases d...
journal_title：British journal of cancer
pub_type： 杂志文章,多中心研究
doi：10.1038/bjc.1993.147
更新日期：1993-04-01 00:00:00
abstract：:Tumour recurrence and metastases of hepatocellular carcinoma (HCC) after hepatectomy are the major obstacles of long-term survival. The present study investigated the clinicopathological significance of a possible metastasis regulator Six1 in HCC patients who were undergone hepatectomy. Seventy-two pairs of RNA and 10...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6603399
更新日期：2006-10-23 00:00:00
abstract：:In the BUPA study, a prospective study of 22,000 men attending a screening centre in London, the mean serum cholesterol level of the 267 men who developed cancer was 6.66 mmol l-1, not significantly different from the mean level of 6.72 mmol l-1 among the 525 unaffected controls matched for age, smoking history and th...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1989.198
更新日期：1989-06-01 00:00:00
abstract：BACKGROUND:Enzastaurin, an oral serine-threonine kinase inhibitor, was initially developed as an ATP-competitive selective inhibitor against protein kinase Cβ. However, the mechanism by which enzastaurin contributes to tumourigenesis remains unclear. METHODS:We analysed the anti-tumour effects of enzastaurin in 22 lun...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2012.7
更新日期：2012-02-28 00:00:00
abstract：BACKGROUND:Heterogeneity and low incidence comprise the biggest challenge in sarcoma diagnosis and treatment. Chemotherapy, although efficient for some sarcoma subtypes, generally results in poor clinical responses and is mostly recommended for advanced disease. Specific genomic aberrations have been identified in some...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/s41416-018-0359-4
更新日期：2019-02-01 00:00:00
abstract：:Cellular adhesion molecules have been implicated in tumour progression and metastasis. This study examines for the first time the serum concentrations of circulating VCAM-1 and E-selectin in a consecutive series of 110 cancer patients seen in a general medical oncology clinic, and confirms and extends previous studies...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1993.298
更新日期：1993-07-01 00:00:00
abstract：:The presence or absence of lymphocytic mucopolysaccharides (MPS) is studied in 223 subjects: 100 normals (controls); 8 cancer patients cured for more than 6 years; 30 cancer patients at the start of their treatment; and 85 relatives of first degree consanguinity of these last patients. The data are studied by statisti...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1973.147
更新日期：1973-09-01 00:00:00
